Treatment of Hepatitis C in children

Paloma Jara; Loreto Hierro

Expert Rev Gastroenterol Hepatol. 2010;4(1):51-61.

Expert Commentary

Current treatment (PEG-IFN-α plus ribavirin) in children with chronic hepatitis C should be managed by pediatric specialists. Many individual and family variables determine the appropriate time to initiate treatment. Mid-childhood age before adolescence is preferable. Side effects are usually well tolerated, but severe adverse events may occur in a low number of children. The near complete efficacy in favorable genotypes, and the early stopping rules for genotype 1 cases shifts the balance toward applying treatment to children, although new drug investigation is needed. The mild disease that children usually present makes safer the initiation of studies once efficacy and toxicity profiles of new drugs have been assessed in adult patients.

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Table 1. Liver damage in children with chronic hepatitis C.
Study	Country	Children (n)	Age at biopsy (years)	Comorbid conditions (%)	Scoring system	Grade, activity (0–18)	Stage Ishak 0–6, Knodell 0–4	Cirrhosis	Factors associated with fibrosis progression	Ref.
Iorio et al. (2005)	Italy	64	8.2 (2–14)	None	Ishak	Median: 4.4 Range: 1–8	Median: 1.6	0	Age or duration not related to fibrosis	^[31]
Mohan et al. (2007)	USA	42	15 ± 1.8 (cohort) 8.8 ± 5 (referral)	26	Knodell	71% mild (0–8), 5% severe (>13)	88% mild (0–1)	0 initial, 14% in follow up	Age of infection shows positive correlation with fibrosis (in referral group)	^[32]
Harris et al. (2007)	UK	98	14 ± 3.5	54	Ishak	Median: 3 Range: 1–7	Median: 1 Range: 0–6	3%	Comorbid conditions, OR: 7.1 Duration of infection in children with comorbidities Female, OR: 0.31	^[33]
Jara et al. (2003)	Spain–Italy–Belgium	92	1–17	None	Ishak	Mean ± SD: 3.9 ± 2, 76% mild (0–6)	1.6 ± 1.3	1%	Age > 15 years	^[26]
Goodman et al. (2008)	PEDS-C USA	121	Mean 9.8	No	Knodell	Mean: 5.1 59% mild, 3% severe	80% some fibrosis	2%	Fibrosis scores correlated with inflammation, but not with age Overweight	^[34]

OR: Odds ratio; PEDS-C: PEG-interferon with or without ribavirin in children with chronic hepatitis C trial; SD: Standard deviation.

Table 2. Efficacy of combined treatment in children.
Study	Treatment schedule	Children (n)	SVR overall (%)	SVR genotype 1	SVR genotype 2&3	SVR parenteral	SVR vertical	SVR		Ref.
Study	Treatment schedule	Children (n)	SVR overall (%)	SVR genotype 1	SVR genotype 2&3	SVR parenteral	SVR vertical	Age <12 years	Age >12 years	Ref.
Wirth et al. (2002)	IFN-α-2b 3–5 MU/m² three-times weekly + RBV 15 mg/kg/day	41	61	18/34 (52.9%)	7/7 (100%)	9/16 (56%)	14/21 (66%)			^[51]
Gonzalez-Peralta et al. (2005)	IFN-α-2b 3 MU/m² three-times weekly + RBV 15 mg/kg/day	118	46	33/92 (36%)	21/25 (84%)			43/75 (57%)	11/43 (26%)	^[52]
Wirth et al. (2005)	PEG- IFN-α-2b 1.5 µg/kg/week + RBV 15 mg/kg/day	61	59	22/46 (47.8%)	13/13 (100%)	19/27 (70.4%)	12/25 (48%)			^[62]
Jara et al. (2008)	IFN-α-2b 1 µg/kg/week + RBV 15 mg/kg/day	30	50	12/26 (46%)	3/3 (100%)	7/9 (78%)	8/21 (38%)	9/20 (45%)	6/10 (60%)	^[61]
P02538 study (2008)	IFN-α-2b 60 µg/kg/week + RBV 15 mg/kg/day	107	64	53%	93%					^[58]
PEDS-C trial (2008)	IFN-α-2a 180 µg/1.73 m²/week + RBV 15 mg/kg/day	55	53	47%	Non-1: 80%					^[60]

PEDS-C: PEG-interferon with or without ribavirin in children with chronic hepatitis C trial; RBV: Ribavirin; SVR: Sustained virologic response.

Table 3. Adverse events of combined treatment in children.
Study	Treatment schedule	Children (n)	Discontinuation due to AE	Reduced IFN due to AE (%)	Number of severe AE	Severe AE (n)	Permanent AE (n)	Ref.
Wirth et al. (2002)	IFN-α-2b 3–5 MU/m² three-times weekly + RBV 15 mg/kg/day	41	1 (2.4%)	0	4	Anemia: 1 Hypothyroidism: 3	0	^[51]
Gonzalez-Peralta et al. (2005)	IFN-α-2b 3 MU/m² three-times weekly + RBV 15 mg/kg/day	118	8 (7%)	31	6	Suicide attempt: 1 Suicide ideation: 1 Depression: 1 Hypothyroidism: 2 Hypothyroidism + diabetes: 1	1 hypothyroidism + diabetes	^[52]
Wirth et al. (2005)	PEG- IFN-α-2b 1.5 µg/kg/week + RBV 15 mg/kg/day	61	1 (1.6%)	5	7	Injection site reaction: 1 Hypothyroidism: 5 Diabetes: 1	1 diabetes	^[62]
Jara et al. (2008)	PEG-IFN-α-2b 1 µg/kg/week + RBV 15 mg/kg/day	30	3 (10%)	23	3	High fever: 1 Hyperthyroidism: 2	0	^[61]

AE: Adverse event; RBV: Ribavirin.

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